The Abundance of Long Intergenic Non-coding RNA 01087 Differentiates Luminal From Triple-negative Breast Cancer Patients and Predicts Their Clinical Outcome

Abstract Background The molecular complexity of human breast cancer (BC) is one of the current challenges for the clinical management of the disease. The identification of subtype-specific biomarkers, such as long non-coding RNAs (lncRNAs), is currently investigated to improve BC patient’s stratification, early detection and disease monitoring. Methods High-throughput sequencing approach of rRNA-depleted RNA samples extracted from 61 laser-microdissected breast tissues, supported by in silico analyses relying on TCGA database (n = 813), were performed to define a specific signature of lncRNAs in the different BC subtypes. Focusing on the long intergenic non-coding RNA 01087 (LINC01087), we estimated its prognostic value using Kaplan-Meier Plotter Database, together with its association with clinical parameters and the histological tumor type within the TCGA cohort of BC patients. cBioPortal data were used to evaluate the expression level of LINC01087 according to the mutational status of TP53, BRCA1 and BRCA2 in BC patients. TCGA samples of triple-negative BC (TNBC) and luminal BCs have been segregated according to the expression level of LINC01087 for comparative analysis of the transcriptomic profiles to identify genes modulated upon variation of the level of LINC01087. GO, KEGG and REACTOME functional annotation and enrichment analyses of these modulated genes were conducted, and their protein-protein interaction networks built using STRING database. Results We identified the involvement of LINC01087 in breast oncogenesis. LINC01087 appeared significantly downregulated in TNBCs and upregulated in the luminal BC subtypes in comparison to mammary samples from cancer-free woman and matched normal cancer tissue pairs. Deregulation of LINC01087 allowed to accurately distinguish luminal and TNBC specimens, independently of the clinicopathological parameters, of the histological and TP53 or BRCA1/2 mutational status. Moreover, a higher level of LINC01087 expression predicted a better prognosis in luminal BCs, while TNBCs harboring a lower expression of LINC01087 were associated with a reduced relapse-free survival. Furthermore, bioinformatics analyses suggested a putative tumor suppressor activity of LINC01087 through interference with pathways involved in cell survival, proliferation, adhesion, or inflammation. Conclusions The assessment of LINC01087 deregulation in BCs represents a novel and specific biomarker for the diagnosis of luminal BC and TNBC subtypes, and also to predict their clinical outcome.